Significant advances in high-throughput sequencing and new tools for analyzing microbiomes as well as the demonstrated value of microbiome research in human health are driving rapid development in this field. This rapid and exponential increase in microbiome-related studies, however, employs a stochastic, non-standardized approach to microbiome research. As a consequence, a large volume of data has been gathered and interpreted in different ways, not readily comparable among laboratories and therefore, less useful. This must be remedied if microbiome science is to pay a central role in diagnosis and therapy of disease conditions. Because microbial community analysis can be biased by multiple technical factors, e.g., storage conditions, DNA extraction or PCR amplification, reference standards are essential to monitor and evaluate such variables as currently used in clinical chemistry and microbiology. We propose that well characterized, homogeneous and stable reference standards can be used as quality control to routinely monitor the laboratory process and to validate new methods. The results obtained during our Pilot Study indicate that it is feasible to construct a whole genome reference standard that can be homogenized to provide a well-defined microbiome composition that is statistically validated and useful for quality control of microbiome studies. From these results, the development of a reference standard is feasible, with high likelihood of success. We will develop an SOP, optimize the process and scale to commercial quantities the manufacturing of Microbiome Reference Standards (MRS). Each iteration of the manufacturing process will undergo internal validations to assess achieved homogeneity and stability during prolonged storage, as well as data reproducibility. The market for the proposed MRS is a new market in the field of microbiome research. We are not aware of any similar commercial product available. Our initial marketing efforts will be focused on developing key partnerships and developing products that will be sold and distributed through their existing sales channels. The proposed MRS products offers a solution for the unmet need for comprehensive microbiome quality control, addressing the need of the scientific community and NIH Human Microbiome Project. The MRS proposed here, prepared and made available at commercial scale, will provide microbiome practitioners with a much needed, and currently unavailable reference for quality control and validation of microbiomes and serve as gold standard for human microbiomes.